Zirconium-Based Metal–Organic Frameworks as Acriflavine Cargos in the Battle against Coronaviruses─A Theoretical and Experimental Approach
Przemysław J. Jodłowski, Klaudia Dymek, Grzegorz Kurowski, Jolanta Jaśkowska, Wojciech Bury, Marzena Pander, Sylwia Wnorowska, Katarzyna M. Targowska‐Duda, Witold Piskorz, Artur Wnorowski, Anna Boguszewska‐Czubara
Abstract
In this study, we present a complementary approach for obtaining an effective drug, based on acriflavine (ACF) and zirconium-based metal-organic frameworks (MOFs), against SARS-CoV-2. The experimental results showed that acriflavine inhibits the interaction between viral receptor-binding domain (RBD) of spike protein and angiotensin converting enzyme-2 (ACE2) host receptor driving viral cell entry. The prepared ACF@MOF composites exhibited low (MOF-808 and UiO-66) and high (UiO-67 and NU-1000) ACF loadings. The drug release profiles from prepared composites showed different release kinetics depending on the local pore environment. The long-term ACF release with the effective antiviral ACF concentration was observed for all studied ACF@MOF composites. The density functional theory (DFT) calculations allowed us to determine that π-π stacking together with electrostatic interaction plays an important role in acriflavine adsorption and release from ACF@MOF composites. The molecular docking results have shown that acriflavine interacts with several possible binding sites within the RBD and binding site at the RBD/ACE2 interface. The cytotoxicity and ecotoxicity results have confirmed that the prepared ACF@MOF composites may be considered potentially safe for living organisms. The complementary experimental and theoretical results presented in this study have confirmed that the ACF@MOF composites may be considered a potential candidate for the COVID-19 treatment, which makes them good candidates for clinical trials.